DIAGNOSTIC ELECTRON MICROSCOPY AND PEDIATRIC PATHOLOGY

本方案的目的是检查毒性和免疫- 患者中GM-CSF和TNF的调节活性。晚期癌症患者 的 GM-CSF和TNF联合刺激树突状细胞成熟 来自体外的CD 34+骨髓祖细胞。 TNF具有双重 在树突状细胞的成熟中起作用，它上调 GM-CSF受体在骨髓祖细胞上的表达， 成熟为粒细胞。 树突状细胞是最有效的 免疫系统的抗原呈递细胞。他们作为发起人 在器官移植排斥反应中，主要组织相容性限制性T细胞 反应和依赖于T细胞的抗体的形成。 树突状细胞在许多组织中以少量存在， 外周血 本研究将检测TNF和GM-CSF的活性 刺激树突细胞的成熟和功能。 表皮 采用S100染色法和外周血细胞计数法对朗格汉斯细胞进行定量 单核树突状细胞前体树突状CFU测定在甲基 纤维素. 表皮中S100+细胞数较对照组增加一倍（2.55 治疗前为5.98，治疗后为5.98，p = 0.029）。 树突状集落 3例治疗后外周血造血干细胞形成单位增加， 结直肠癌患者，但患者中未增加。与 黑素瘤 本协议的主要目标是确定 GM-CSF和TNF的组合引起树突细胞的成熟， 增加血液、骨髓和皮肤中的数量， 如果这种增加导致肿瘤消退。

The purpose of this protocol is to examine the toxicity and immuno- modulatory activity of GM-CSF and TNF in pts. with advanced cancer. The combination of GM-CSF and TNF stimulates the maturation of dendritic cells from CD34+ bone marrow progenitor cells in vitro. TNF has a two-fold function in the maturation of dendritic cells, it up-regulates the expression of the GM-CSF receptor on bone marrow progenitors and prevents their maturation into granulocytes. Dendritic cells are the most potent antigen presenting cells of the immune system. They function as initiators in organ transplant rejection, major histocompatibility restricted T cell responses and in the formation of antibodies dependent on T cells. Dendritic cells are found in small numbers in many tissues and in peripheral blood. This study will examine the activity of TNF and GM-CSF to stimulate the maturation and function of dendritic cells. Epidermal Langerhans cells were quantitated by S100 staining and peripheral blood mononuclear dendritic cell precursors by dendritic CFU assay in methy- cellulose. S100+ cells in the epidermis doubled after treatment (2.55 before treatment to 5.98 after treatment, p=0.029). Dendritic colony forming units in peripheral blood were increased after treatment in 3 patients with colorectal cancer but were not increased in pts. with melanoma. The major goal of this protocol is to determine whether the combination of GM-CSF and TNF causes maturation of dendritic cells and increases their number in the blood, bone marrow and skin and to determine if this increase produces tumor regressions.